Stem cell-based therapies are being explored for the treatment of several disease states characterized by damaged tissue. Although stem cells injected into damaged tissue have been shown to at least partially regenerate the tissue, the delivered cells and/or regenerated tissue are subsequently destroyed by the underlying cause of the disease. The development of methods for enhancing the survival of transplanted stem cells/regenerated tissue would therefore be useful for the successful implementation of stem cell regenerative therapy.
Life-threatening and chronic diseases are often characterized by the presence of particular physiological signals. For example, hypoxia is a signal associated with ischemic heart disease, while high blood glucose is a signal for diabetes. Such disease-associated signals directly or indirectly modulate gene expression in cells exposed to the signals. If these signals could be harnessed to activate expression of therapeutic or protective gene products, the success of the stem cell-based therapy might be improved. For example, when engrafted into a heart, stem cells that sense and respond to hypoxia by expressing a cardioprotective gene that promotes the long-term survival of the transplanted stem cells and surrounding tissue in the pathologic (hypoxic) environment would be useful for treating cardiac infarction or for preventing pathology due to cardiac ischemia.